Gómez-López, Sandra;
Alhendi, Ahmed SN;
Przybilla, Moritz J;
Bordeu, Ignacio;
Whiteman, Zoe E;
Butler, Timothy;
Rouhani, Maral J;
... Janes, Sam M; + view all
(2025)
Aberrant basal cell clonal dynamics shape early lung carcinogenesis.
Science
, 388
(6752)
, Article eads9145. 10.1126/science.ads9145.
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Abstract
Preinvasive squamous lung lesions are precursors of lung squamous cell carcinoma (LUSC). The cellular events underlying lesion formation are unknown. Using a carcinogen-induced model of LUSC with no added genetic hits or cell type bias, we find that carcinogen exposure leads to non-neutral competition among basal cells, aberrant clonal expansions, and basal cell mobilization along the airways. Ultimately, preinvasive lesions develop from a few highly mutated clones that dominate most of the bronchial tree. Multi-site sequencing in human patients confirms the presence of clonally related preinvasive lesions across distinct airway regions. Our work identifies a transition in basal cell clonal dynamics, and an associated shift in basal cell fate, as drivers of field cancerization in the lung.
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